Using breath analysis for medical diagnosis is the subject of intense research effort. The non-invasive and real time nature of the measurement in addition to the ability to detect pathogenic changes at the molecular level are main advantages of this approach.
The concentration of specific biomarkers in human breath can be related to a symptom of a particular disease. For example, high concentrations of acetone in exhaled breath is known to be a biomarker of diabetes and of fat burning. The breath of non-diabetics typically contains ˜0.5 parts per million (ppm) acetone. Elevated mean breath acetone concentration of ˜0.8-4.0 ppm has been shown to exist in Type 1 and Type 2 diabetics. Some correlation between acetone concentration in breath and blood glucose levels has been suggested.
Diabetes is one of the most challenging problems for public health worldwide. It is a chronic disorder that affects the body's ability to use sugar as a source of energy, and consequently high blood sugar levels build up in the blood. People with diabetes either do not produce insulin (Insulin deficiency: type 1) or the production of insulin is not sufficient/effective (Insulin resistance: type 2). As a consequence of insulin resistance or deficiency, the human body is unable to use sugar as a source of energy, and therefore the body resorts to breaking down stores of fat and protein instead. This alternative source of fuel ultimately leads to elevated ketone concentration in the blood, including elevated acetone concentration. The acetone concentration in a person's exhaled breath is monotonically related to the concentration of acetone in their blood.
Since no cure is currently available, the condition requires lifelong management. In the case of type 1 diabetes, this includes keeping blood glucose levels within safe levels through frequent insulin injections or a continuous infusion of insulin through an insulin pump. For type 2 diabetes, blood glucose levels are managed through a combination of medication, diet, and exercise or insulin injections if necessary.
Furthermore, a life threatening condition known as diabetic ketoacidosis (DKA) can develop when very high levels of acetone in the blood are present. If this condition is not treated it can lead to diabetic coma or even death. Diabetic ketoacidosis accounts for around 50% of all diabetes-related hospital admissions in people with type 1 diabetes.
In order to manage blood glucose levels and prevent DKA, people with diabetes are required to frequently (typically 4 to 10 times a day) measure their blood glucose and in some cases their blood ketone levels. This is done using a small blood sample obtained through a painful and troublesome procedure requiring patients to prick their fingers each time a test is required.
Similar procedures may be used for diagnosis and screening. In the primary diagnosis a urine sample may be tested for the presence of ketones and/or glucose. Although this test is high in specificity, it has a very low sensitivity and is generally inconvenient.
In summary, current diabetes diagnosis and management methods/procedures generally have low sensitivity, are inconvenient, are painful to patients, and are time and money consuming. Therefore, extensive efforts worldwide are being devoted to find effective non-invasive methods for diabetes diagnosis and management.
Measurement of the concentration of acetone in a person's exhaled breath may be used as a means for diabetes diagnosis and diabetes management. However, due to the requirement to measure small acetone concentrations (typically in the range 0.1-10 ppm) and the presence of hundreds of different Volatile Organic Compounds (VOCs) in the human breath, no portable reliable acetone breath analyser for diabetes is currently available on the market.
For non-diabetic people, elevated breath acetone is mainly due to fat burning as a result of insufficient intake of carbohydrates to meet the metabolic needs of the body [O. B. Crofford et al., Acetone in breath and blood, Trans Am Clin Climatol Assoc. 1977; 88: 128-139]. Hence, if a patient is trying to lose weight this is a very useful index of success and can be used to encourage the patient.
Conventional breath analysis is conducted using gas chromatography coupled with a detection method, such as flame ionisation, ion mobility spectrometer, and mass spectrometer. These methods require bulky and expensive equipment as well as skilled operators, and therefore are not suitable for real time point-of-care testing.
Recently, cavity ringdown spectroscopy was used to measure the concentration of acetone in exhaled breath using light with ultraviolet (UV) or near-infrared (NIR) wavelengths [Wang et al, US20040137637 A1 (published Jul. 15, 2004); Wang et al., Measurement Science and Technology 19 105604 (published Aug. 27, 2008)]. This technique requires the use of lasers which are expensive components, especially at UV and NIR frequencies.
Graham et al., WO2011117572A1 (published Sep. 29, 2009) teaches use of a broadband NIR light source for breath acetone detection using a resonant optical cavity. This design determines acetone concentration in exhaled breath from a measurement of the absorption spectrum of the breath (i.e. the dependence of absorption in the breath on wavelength) at NIR wavelengths where acetone exhibits characteristic absorption. A broadband NIR light source is chosen which emits light over a range of wavelengths which is significantly broader than the range of wavelengths of a particular absorption band for acetone. The absorption spectrum is then measured using expensive components such as tunable filters, spectrometers, or gratings. Unfortunately, many other components in breath—such as VOCs or water vapour—exhibit strong absorption of infrared light which makes measurement at these wavelengths difficult and prone to absorption interferences.
Although metal oxide semiconductor sensors can be used for acetone detection, they suffer from poorly understood detection mechanism as well as low sensitivity. More importantly, they suffer from absorption interferences from other volatile organic compounds present in both air and breath, making them poor in terms of specificity [Kanan et al., Sensors 2009, 9, 8158-8196, published Oct. 16, 2009].
Other breath acetone detection methods include Massick, U.S. Pat. No. 7,790,467B1 (issued Sep. 7, 2010), which describes an indirect method based on the use of a diode laser emitting infrared light to detect a reaction by-product between acetone and hydrogen halide. Goldstein et al., U.S. Pat. No. 6,479,019B1 (issued Nov. 12, 2002) describes a chemo-optical sensor where light absorption or transmission is a function of reaction with a target gas molecule such as acetone or other chemical. These methods are either complicated, have low detection limit, or suffer from low specificity.
An important issue with many of the above breath analysis methods is interference with other VOCs present either in ambient air or breath. Such interferences affect the sensitivity and specificity of the breath analyser.
Another related prior art is patent application Harely, US20100061885 A1 (published on Mar. 11, 2010), which discusses an instrument for determining Ozone concentration using a UV light source including LEDs.